The nose is the most sophisticated chemical sensor ever devised. In less than a second a nose can detect and distinguish between vast numbers of chemicals. Olfaction works via odorants being detected by G-protein coupled receptors (GPCRs). The goal of this application is to develop a sensor for bioagents that mirrors the sensitivity, specificity and speed of the olfactory system. In addition to odorants, GPCRs are used by the body to detect photons, ions, sugars, biogenic amines, lipids, peptides and proteins. This apparent unrestricted nature of ligands to GPCRs suggests that they can be used to detect a broad range of chemicals including bioagents. The approach to developing a GPCR-based sensor is to subject a defined set of GPCRs to directed evolution in vitro via massive mutagenesis and subsequent screening for receptors with the appropriate specificities. The screening process uses a melanophore-based system for high-throughput identification of relevant receptors. In the future, optimized receptors will be arrayed and utilized in a device to which samples are introduced and results displayed via changes in spectrophotometric or fluorescent signals.